On the use of sex steroids in women during the COVID-19 pandemic

The consensus position statement of professional medical associations: Ukrainian Society of Gynecological Endocrinology, Association of Obstetricians-Gynecologists of Ukraine, Association of Pharmacologists of Ukraine, Association of Anesthesiologists of Ukraine, Association of Vascular Surgeons, Phlebologists and Angiologists of Ukraine

Authors

  • T.F. Tatarchuk NAMS of Ukraine, Ukraine https://orcid.org/0000-0002-5498-4143
  • Z.M. Dubossarska Dnipro State Medical University, Ukraine
  • V.I. Pyrohova Danylo Halytsky Lviv National Medical University, Ukraine
  • N.Y. Pedachenko Shupyk National Healthcare University of Ukraine, Ukraine
  • T.M. Tutchenko SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”, Ukraine
  • O.О. Yefimenko SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”, Ukraine
  • N.V. Kosei SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”, Ukraine
  • Y.O. Dubossarska Dnipro State Medical University, Ukraine
  • K.L. Shatylovych Danylo Halytsky Lviv National Medical University, Ukraine
  • V.M. Zaporozhan Odesa National Medical University, Ukraine
  • V.V. Kaminskyi Shupyk National Healthcare University of Ukraine, Ukraine
  • G.V. Zaichenko O.O. Bogomolets National Medical University, Ukraine
  • S.A. Dubrov O.O. Bogomolets National Medical University, Ukraine
  • L.M. Chernukha O.O. Shalimov National Institute of Surgery and Transplantology of the NAMS of Ukraine, Ukraine

DOI:

https://doi.org/10.18370/2309-4117.2021.58.9-16

Keywords:

combined hormonal contraceptives, menopausal hormonal therapy, unregistered compounded bioidentical hormonal agents, venous thromboembolism, angiotensin-converting enzyme 2 receptors

Abstract

The document was approved at an expanded meeting of the Ukrainian Society of Gynecological Endocrinology with the involvement of all board members and representatives of the Association of Obstetricians-Gynecologists of Ukraine, the Association of Pharmacologists of Ukraine, the Association of Anesthesiologists of Ukraine, as well during the Third Ukrainian School of Gynecological and Reproductive Endocrinology with international participation ISGE 19–20.03.21.
The COVID-19 pandemic has significantly impacted medical practice, in terms of organizational and clinical practices, posing a number of complex and contradictory challenges for professionals.
This document is the result of the systematization of scientific data available by March 2021 and recommendations of international medical and specialized professional societies on controversial clinical issues in gynecological practice caused by the COVID-19 pandemic, as well as certain issues of safety and ratio of using hormonal drugs. The involvement of experts from professional associations of the obstetric and gynecological field, pharmacology, anesthesiology and vascular surgery and phlebology in the working group made it possible to formulate clinically justified provisions of the position.
The position includes three thematic sections: “On the use of estrogen-containing combined hormonal contraceptives (CHC) during the COVID-19 pandemic”; “On the use of menopausal hormone therapy (MHT) during the COVID-19 pandemic”; “On the issue of unregistered compounded bioidentical hormones”.
At the beginning of each thematic section, the main conclusions of the consensus position of professional medical associations are presented. According to the data available by March 2021, there is no reason to limit the use of CHC or MHT in healthy women (currently not having COVID-19). The question of CHC or MHT discontinuing or switching to other forms by women with COVID-19 should be decided depending on the severity of the disease, the total set of risk factors for thromboembolic complications and other individual characteristics of the clinical situation. Further research will provide elaboration of more detailed algorithms. Physicians need to be vigilant about the safety of compounded Bioidentical Hormonal Therapy (cBHT) in any dosage form (including pellets), especially during the COVID-19 pandemic, given the unexplored systemic effects and therefore the potential risks. Preference should be given to officially licensed medicinal products with a well-studied safety profile and clinical effects, the use of which is authorized by doctor's prescription and supported by clinical protocols and guidelines.

Author Biographies

T.F. Tatarchuk, NAMS of Ukraine

MD, professor, corresponding member of the NAMS of Ukraine, deputy director for research work, head of the Endocrine Gynecology Department, SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”, chief researcher, Department of Reproductive Health, SSI “CIMT of the NAS of Ukraine”, President of the Ukrainian Society of Gynecological Endocrinology, Kyiv

Z.M. Dubossarska, Dnipro State Medical University

MD, professor, Department of Family Medicine, Faculty of Postgraduate Education, Vice President of the Ukrainian Society of Gynecological Endocrinology, Dnipro

V.I. Pyrohova, Danylo Halytsky Lviv National Medical University

MD, head of the Obstetrics, Gynaecology and Perinatology Department, Faculty of Postgraduate Education, Vice President of the Ukrainian Society of Gynecological Endocrinology, Lviv

N.Y. Pedachenko, Shupyk National Healthcare University of Ukraine

MD, professor at the Department of Obstetrics, Gynecology and Perinatology

T.M. Tutchenko, SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”

PhD, senior researcher of the Endocrine Gynecology Department, Department of Reproductive Health, SSI “CIMT of the NAS of Ukraine", Kyiv

O.О. Yefimenko, SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”

PhD, senior researcher at the Endocrine Gynecology Department, Department of Reproductive Health, SSI “CIMT of the NAS of Ukraine”, Kyiv

N.V. Kosei, SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”

MD, professor, chief researcher, Endocrine Gynecology Department, head of Department of Reproductive Health, SSI “CIMT of the NAS of Ukraine", Kyiv

Y.O. Dubossarska, Dnipro State Medical University

MD, professor, head of the Obstetrics, Gynecology and Perinatology Department, Faculty of Postgraduate Education

K.L. Shatylovych, Danylo Halytsky Lviv National Medical University

MD, professor at the Obstetrics and Gynecology Department

V.M. Zaporozhan, Odesa National Medical University

Academician of NAMS of Ukraine, MD, professor, Rector of Odesa National Medical University, President of the Association of Obstetricians and Gynecologists of Ukraine, Odesa

V.V. Kaminskyi, Shupyk National Healthcare University of Ukraine

MD, professor, corresponding member of the NAMS of Ukraine, head of the Obstetrics, Gynecology and Reproductology Department, chairman of the Executive Committee of the Association of Obstetricians and Gynecologists of Ukraine, Kyiv

G.V. Zaichenko, O.O. Bogomolets National Medical University

MD, professor, head of the Department of Pharmacology

S.A. Dubrov, O.O. Bogomolets National Medical University

MD, professor, Department of Anesthesiology and Intensive Care, Chief Specialist in anesthesiology of the Ministry of Health of Ukraine, President of the Association of Anesthesiologists of Ukraine, Kyiv

L.M. Chernukha, O.O. Shalimov National Institute of Surgery and Transplantology of the NAMS of Ukraine

MD, professor, chief researcher, Department of Vascular Surgery, Chief phlebologist of Ukraine, Vice President of the Association of Vascular Surgeons, Phlebologists and Angiologists of Ukraine, Kyiv

References

  1. World Health Organization. Pulse survey on continuity of essential health services during the COVID-19 pandemic: interim report (2020). Available from: [https://www.who.int/publications/i/item/WHO-2019-nCoV-EHS_continuity-survey-2020.1]/.
  2. United Nations Population Fund. Three things you need to know about contraceptives and COVID-19. Available from: [https://www.unfpa.org/news/three-things-you-need-know-about-contraceptives-and-covid-19].
  3. Faculty of Sexual and Reproductive Healthcare. Ensuring provision of Sexual and Reproductive Healthcare (SRH) services during the third COVID-19 lockdown and beyond in the UK. Available from: [https://www.fsrh.org/documents/fsrh-guidance- essential-srh-services--third-covid-19-lockdown/fsrh-guidance- service-provision-c-19-third-lockdown-22-january-2021.pdf].
  4. American college of obstetrician-gynecologists. COVID-19 FAQs for Obstetrician–Gynecologists. Available from: [https://www.acog.org/clinical-information/physician-faqs/covid19-faqs-for-ob-gyns-gynecology].
  5. Jones, R.K. Beyond Birth Control: The Overlooked Benefits Of Oral Contraceptive Pills. Gutt Macher Institute (2011).
  6. Lete, I.“Combined hormonal contraception and COVID-19.” The European Journal of Contraception & Reproductive Health Care (2021). DOI: 10.1080/13625187.2020.1867845
  7. Cagnacci, A., Xholli, A. “Age-related difference in the rate of COVID-19 mortality in women versus men.” Am J Obstet Gynecol (2020). DOI: 10.1016/j.ajog.2020.05.039
  8. Scavini, M., Piemonti, L. “Gender and age effects on the rates of infection and deaths in individuals with confirmed SARS-CoV-2 infection in six European countries.” Available from: [https://ssrn.com/abstract=3576790].
  9. Cheng, H., et al. “Organ-protective effect of angiotensin-converting enzyme 2 and its effect on the prognosis of COVID-19.” J Med Virol 92.7 (2020): 726–30.
  10. Kostinov, M.P., ed. Basis of immunorehabilitation for new coronavirus infection (COVID-19). A guide for doctors. Moscow. Group MDV (2020): 112 p.
  11. Cagnacci, A., Bonaccorsi, G., Gambacciani, M.; board of the Italian Menopause Society. “Reflections and recommendations on the COVID-19 pandemic: Should hormone therapy be discontinued?” Maturitas 138 (2020): 76–7.
  12. Mauvais-Jarvis, F., Sabra L. Klein, S.L., Levin, E.R. “Estradiol, Progesterone, Immunomodulation, and COVID-19 Outcomes.” Endocrinology 161.9 (2020): 1–8.
  13. Bourguignon, A., Beaulieu, C., Belkaid, W., et al. “Incidence of thrombotic outcomes for patients hospitalized and discharged after COVID-19 infection.” Thromb Res 196 (2020): 491–3.
  14. Practice Committee of the American Society for Reproductive Medicine. ”Combined hormonal contraception and the risk of venous thromboembolism: a guideline.” Fertility and sterility 107.1 (2017): 43–51.
  15. Sitruk-Ware, R. “Hormonal contraception and thrombosis.” Fertil Steril 106 (2016): 1289–94.
  16. Ferreira-Filho, E.S., et al. “Contraception and reproductive planning during the COVID-19 pandemic.” Expert Review of Clinical Pharmacology 13.6 (2020): 615–22. DOI: 10.1080/17512433.2020.1782738
  17. Wray, S., Arrowsmith, S. ”The physiological mechanisms of the sex-based difference in outcomes of COVID19 infection.” Frontiers in Physiology 12 (2021): 71.
  18. Grandi, G., Facchinetti, F., Bitzer, J. “The gendered impact of coronavirus disease(COVID-19): do estrogens play a role?” The European Journal of Contraception & Reproductive Health Care 25.3 (2020): 233–4.
  19. Agrawal, H., et al. “An assessment on impact of COVID-19 infection in a gender specific manner.” Stem cell reviews and reports 17.1 (2021): 94–112. DOI: 10.1007/s12015-020-10048-z
  20. Hamzaoglu, K., Erel, C.T. “Should estrogen be used in the co-treatment of COVID-19 patients? What is the rationale?” Maturitas 140 (2020): 80.
  21. Breithaupt-Faloppa, A.C., de Jesus Correia, C., Máximo Prado, C., et al. “17β-Estradiol, a potential ally to alleviate SARS-CoV-2 infection.” Clinics (Sao Paulo) 75 (2020): e1980.
  22. Chanana, N., Palmo, T., Sharma, K., et al. “Sex-derived attributes contributing to SARS-CoV-2 mortality.” Am J Physiol Endocrinol Metab 319.3 (2020): E562–E567.
  23. Lete, I., Chabbert-Buffet, N., Jamin, C., et al. “Haemostatic and metabolic impact of estradiol pills and drospirenone-containing ethinylestradiol pills vs. levonorgestrel- containing ethinylestradiol pills: a literature review.” Eur J Contracept Reprod Health Care 20.5 (2015): 329–43.
  24. Costeira, R., Lee, K.A., Murray, B., et al. Estrogen and COVID-19 symptoms: associations in women from the COVID Symptom Study. medRxiv (2020).
  25. World Health Organization. Contraception/Family planning and COVID-19 (2020). Available from: [https://www.who.int/news-room/q-a-detail/contraception-familyplanning- and-covid-19].
  26. Faculty of Sexual and Reproductive Healthcare. FSRH CEU clinical advice to support provision of effective contraception during the COVID-19 outbreak (2020).
  27. Faculty of Sexual and Reproductive Healthcare. Provision of contraception during the COVID-19 pandemic: FSRH update and overview statement (2020)
  28. Faculty of Sexual and Reproductive Healthcare. FSRH Clinical Effectiveness Unit Statement: Use of combined hormonal contraception during the Covid-19 pandemic (2020).
  29. Ramírez, I., De la Viuda, E., Baquedanoet L., et al. “Managing thromboembolic risk with menopausal hormone therapy and hormonal contraception in the COVID-19 pandemic: Recommendations from the Spanish Menopause Society, Sociedad Española de Ginecología y Obstetricia and Sociedad Española de Trombosis y Hemostasia.” Maturitas 137 (2020): 57–62.
  30. Collège National des Enseignants de GynécologieMédicale; L’Unitéd’Hémostase Clinique de Cochin. Prévention du risque thromboembolique veineux chez les femmes COVID + non hospitalisées utilisant un traitement hormonal (Contraception, Traitement hormonal de ménopause, Tamoxifène) (2020).
  31. Pickar, J.H., et al. ”Safety and benefit considerations for menopausal hormone therapy.” Expert opinion on drug safety 16.8 (2017): 941–54.
  32. Roncon, L., et al. “Incidence of acute Pulmonary Embolism in COVID-19 patients: systematic review and meta-analysis. Pulmonary Embolism and COVID-19.” Europe an journal of internal medicine (2020).
  33. Porfidia, A., et al. “Venous thromboembolism in patients with COVID-19: Systematic review and meta-analysis.” Thrombosis research 196 (2020): 67–74.
  34. Rovinski, D., et al. “Risk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: A systematic review and meta-analysis.” Thrombosis research 168 (2018): 83–95.
  35. Vinogradova, Y., Coupland, C., Hippisley-Cox, J. “Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases.” BMJ 364 (2019).
  36. Scarabin, P-Y. “Progestogens and venous thromboembolism in menopausal women: an updated oral versus transdermal estrogen meta-analysis.” Climacteric 21.4 (2018): 341–5.
  37. Ding, T., et al. “Potential influence of menstrual status and sex hormones on female SARS-CoV-2 infection: a cross-sectional study from multicentre in Wuhan, China.” Clinical Infectious Diseases (2020).
  38. Al-Lami, R.A., et al. “Sex hormones and novel corona virus infectious disease (COVID-19).” Mayo Clinic Proceedings. Elsevier (2020).
  39. Haitao, T., et al. “COVID-19 and sex differences: mechanisms and biomarkers.” Mayo Clinic Proceedings. Elsevier (2020).
  40. Ancochea, J., et al. “Evidence of gender differences in the diagnosis and management of coronavirus disease 2019 patients: An analysis of electronic health records using natural language processing and machine learning.” Journal of Women's Health 30.3 (2021): 393–404.
  41. Baber, R.J., et al. “IMS Recommendations on women's midlife health and menopause hormone therapy.” Climacteric 19 (2016): 109–50.
  42. The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. “The 2017 hormone therapy position statement of The North American Menopause Society.” Menopause 24 (2017): 728–53.
  43. Lumsden, M.A. “The NICE Guideline - Menopause: diagnosis and management.” Climacteric 19.5 (2016): 426–9. DOI: 10.1080/13697137.2016.1222483
  44. de Villiers, T., Tatarchuk, T.F., et al. “National consensus on the management of patients in menopause.” Reproductive endocrinology 27 (2016): 8–25.
  45. Primary Care Women’s Health Forum. How to manage HRT provision without face to face consultations during COVID-19 healthcare restrictions. Available from: [https://pcwhf.co.uk/wp-content/uploads/2020/05/PCWHF-Menopause- Management-remote-consultation-tool_V4.pdf].
  46. Seeland, U., Coluzzi, F., Simmaco, M., et al. “Evidence for treatment with estradiol for women with SARS-CoV-2 infection.” BMC Med 18 (2020): 369. DOI: 10.1186/s12916-020-01851-z
  47. Taneja, V. “Sex hormones determine immune response.” Frontiers in immunology 9 (2018): 1931.
  48. Habib, P., et al. “Estrogen serum concentration affects blood immune cell composition and polarization in human females under controlled ovarian stimulation.” The Journal of steroid biochemistry and molecular biology 178 (2018): 340–7.
  49. Medina-Estrada, I., et al. “Immunomodulatory effects of 17β-estradiol on epithelial cells during bacterial infections.” Journal of Immunology Research 2018 (2018).
  50. Breithaupt-Faloppa, A.C., et al. “17β-Estradiol, a potential ally to alleviate SARS-CoV-2 infection.” Clinics 75 (2020).
  51. Khan, N. “Possible protective role of 17β-estradiol against COVID-19.” Journal of allergy and infectious diseases 1.2 (2020): 38.
  52. Cevik, M., et al. “Virology, transmission, and pathogenesis of SARS-CoV-2.” BMJ 371 (2020).
  53. Foresta, C., Rocca, M.S., Di Nisio, A. “Gender susceptibility to COVID-19: a review of the putative role of sex hormones and X chromosome.” J Endocrinol Invest (2020).
  54. La Vignera, S., Cannarella, R., Condorelli, R.A., et al. “Sex-specific SARS-CoV-2 mortality: among hormone-modulated ACE2 expression, risk of venous thromboembolism and hypovitaminosis D.” Int J Mol Sci 21.8 (2020).
  55. Whelan, A.M., Jurgens, T.M., Trinacty, M. “Defining bioidentical hormones for menopause-related symptoms.” PharmacyPractice 9.1 (2011): 16.
  56. American Society for Reproductive Medicine Practice Committee. “Compounded bioidentical menopausal hormone therapy.” Fertil Steril 98.2 (2012): 308–12.
  57. Panay, N., Medical Advisory Council of the British Menopause Society. “BMS – Consensus statement: bioidentical HRT.” Post reproductive health 25.2 (2019): 61–3.
  58. Australasian Menopause Society. Bioidentical custom compounded hormone therapy. Available from: [https://www.menopause.org.au/hp/informationsheets/212-bioidentical-hormones-for-menopausalsymptoms]
  59. Pinkerton, J.V., et al. “The National Academies of Science, Engineering, and Medicine (NASEM) Report on Compounded Bioidentical Hormone Therapy.” Menopause 27.11 (2020): 1199–201.
  60. Santoro, N., Braunstein, G.D., Butts, C.L., et al. “Compounded bioidentical hormones in endocrinology practice: an Endocrine Society Scientific Statement.” J Clin Endocrinol Metab 101.4 (2016): 1318–43.
  61. Davis, R., Batur, P., Thacker, H.L. “Risks and effectiveness of compounded bioidentical hormone therapy: a case series.” Journal of Women's Health 23.8 (2014): 642–8.

Published

2021-05-27

How to Cite

Tatarchuk, T., Dubossarska, Z., Pyrohova, V., Pedachenko, N., Tutchenko, T., Yefimenko, O., Kosei, N., Dubossarska, Y., Shatylovych, K., Zaporozhan, V., Kaminskyi, V., Zaichenko, G., Dubrov, S., & Chernukha, L. (2021). On the use of sex steroids in women during the COVID-19 pandemic: The consensus position statement of professional medical associations: Ukrainian Society of Gynecological Endocrinology, Association of Obstetricians-Gynecologists of Ukraine, Association of Pharmacologists of Ukraine, Association of Anesthesiologists of Ukraine, Association of Vascular Surgeons, Phlebologists and Angiologists of Ukraine. REPRODUCTIVE ENDOCRINOLOGY, (58), 9–16. https://doi.org/10.18370/2309-4117.2021.58.9-16

Issue

Section

Health care